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Benor A, Decherney A. Gonadotropin-Releasing Hormone (GnRH) Agonists Do Not Protect Ovarian Function in Patients Undergoing Stem Cell Transplants. Cureus 2024; 16:e58387. [PMID: 38756303 PMCID: PMC11097921 DOI: 10.7759/cureus.58387] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/16/2024] [Indexed: 05/18/2024] Open
Abstract
Introduction Medical indications for fertility preservation include any malignancy, chronic illness, or disease that would require gonadotoxic chemotherapy or radiation (conditioning regimens), which would impede a woman's ability to conceive in the future. Thus, any patient who plans to undergo a gonadotoxic regimen is advised to cryopreserve oocytes or embryos, which can be used in the future at the patient's convenience. Attempts have been made to suppress ovarian function with gonadotropin-releasing hormone agonists (GnRH-a) to induce ovarian quiescence and, thereby, theoretically limit the gonadotoxic impact on the follicular pool. We explored the use of leuprolide (a type of GnRH-a) in preventing primary ovarian insufficiency (POI) in a cohort study of patients who underwent hematopoietic stem cell transplants (HSCT) at the National Institutes of Health (NIH); since the conditioning regimens for HSCT include cyclophosphamide and other gonadotoxic therapies, we hypothesized that GnRH-a would be ineffective in preventing POI. Methods We assessed patients who underwent fertility preservation prior to their stem cell transplant, as their follicular-stimulating hormone (FSH) levels were evaluated prior to and post-chemotherapy. Twenty-nine patients who underwent hormonal evaluation prior to and post-chemotherapy were included. The control group did not receive GnRH-a prior to chemotherapy, while the treatment group did receive GnRH-a pre-chemotherapy. Results Our data revealed that 80% of the control group had menopausal levels post-chemotherapy, while 91% of the treatment group still had menopausal levels post-chemotherapy (p=0.33). Conclusions Thus, our hypothesis that GnRH-a is ineffective in reducing the risk of POI in a cohort of patients who receive conditioning regimens for HSCT was confirmed.
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Affiliation(s)
- Ariel Benor
- Reproductive Endocrinology and Infertility, National Institutes of Health, Bethesda, USA
| | - Alan Decherney
- Reproductive Endocrinology and Infertility, National Institutes of Health, Bethesda, USA
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Gao X, Wang B, Huang Y, Wu M, Li Y, Li Y, Zhu X, Wu M. Role of the Nrf2 Signaling Pathway in Ovarian Aging: Potential Mechanism and Protective Strategies. Int J Mol Sci 2023; 24:13327. [PMID: 37686132 PMCID: PMC10488162 DOI: 10.3390/ijms241713327] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2023] [Revised: 08/21/2023] [Accepted: 08/23/2023] [Indexed: 09/10/2023] Open
Abstract
The ovary holds a significant role as a reproductive endocrine organ in women, and its aging process bears implications such as menopause, decreased fertility, and long-term health risks including osteoporosis, cardiovascular disorders, and cognitive decline. The phenomenon of oxidative stress is tightly linked to the aging metabolic processes. More and more studies have demonstrated that oxidative stress impacts both physiologic and pathologic ovarian aging, and the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway plays a crucial role in regulating the antioxidant response. Furthermore, various therapeutic approaches have been identified to ameliorate ovarian aging by modulating the Nrf2 pathway. This review summarizes the important role of the Nrf2/ Kelch-like ECH-associated protein 1 (Keap1) signaling pathway in regulating oxidative stress and influencing ovarian aging. Additionally, it highlights the therapeutic strategies aimed at targeting the Nrf2/Keap1 pathway.
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Affiliation(s)
- Xiaofan Gao
- National Clinical Research Center for Obstetrical and Gynecological Diseases, Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; (X.G.); (B.W.); (Y.H.); (M.W.); (Y.L.); (Y.L.); (X.Z.)
- Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Wuhan 430030, China
| | - Bo Wang
- National Clinical Research Center for Obstetrical and Gynecological Diseases, Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; (X.G.); (B.W.); (Y.H.); (M.W.); (Y.L.); (Y.L.); (X.Z.)
- Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Wuhan 430030, China
| | - Yibao Huang
- National Clinical Research Center for Obstetrical and Gynecological Diseases, Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; (X.G.); (B.W.); (Y.H.); (M.W.); (Y.L.); (Y.L.); (X.Z.)
- Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Wuhan 430030, China
| | - Meng Wu
- National Clinical Research Center for Obstetrical and Gynecological Diseases, Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; (X.G.); (B.W.); (Y.H.); (M.W.); (Y.L.); (Y.L.); (X.Z.)
- Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Wuhan 430030, China
| | - Yuting Li
- National Clinical Research Center for Obstetrical and Gynecological Diseases, Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; (X.G.); (B.W.); (Y.H.); (M.W.); (Y.L.); (Y.L.); (X.Z.)
- Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Wuhan 430030, China
| | - Yinuo Li
- National Clinical Research Center for Obstetrical and Gynecological Diseases, Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; (X.G.); (B.W.); (Y.H.); (M.W.); (Y.L.); (Y.L.); (X.Z.)
- Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Wuhan 430030, China
| | - Xiaoran Zhu
- National Clinical Research Center for Obstetrical and Gynecological Diseases, Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; (X.G.); (B.W.); (Y.H.); (M.W.); (Y.L.); (Y.L.); (X.Z.)
- Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Wuhan 430030, China
| | - Mingfu Wu
- National Clinical Research Center for Obstetrical and Gynecological Diseases, Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; (X.G.); (B.W.); (Y.H.); (M.W.); (Y.L.); (Y.L.); (X.Z.)
- Key Laboratory of Cancer Invasion and Metastasis, Ministry of Education, Wuhan 430030, China
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Ejaz K, Abid D, Juneau P, Chu J, Hasni S. Use of gonadotropin-releasing hormone agonists for ovarian preservation in patients receiving cyclophosphamide for systemic lupus erythematosus: A meta-analysis. Lupus 2022; 31:1706-1713. [PMID: 36148853 PMCID: PMC9811938 DOI: 10.1177/09612033221128740] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
BACKGROUND Cyclophosphamide (CYC) has known cytotoxic effects on ovarian reserve and has been linked to premature ovarian failure (POF) in systemic lupus erythematosus (SLE). The concurrent use of gonadotropin-releasing hormone agonists (GnRHas) is postulated to preserve ovarian function by reducing the number of follicles exposed to CYC, but there is paucity of data to establish its efficacy. We conducted a meta-analysis to summarize the effect of concurrent GnRHa use in persevering ovarian function and pregnancy. METHODS English language databases of PubMed, Embase, and Cochrane were searched to include studies published between 2000 and 2021. Studies in females with rheumatic diseases receiving concurrent GnRHa and CYC therapy to evaluate ovarian preservation as defined by amenorrhea, follicle stimulating hormone (FSH), anti-mullerian hormone (AMH), or estradiol levels or successful pregnancy were included. We used a fixed effect, exact, Mantel-Haenszel approach to estimate the overall odds ratio (OR) and associated 95% confidence intervals (95% CIs). RESULTS Seven studies with 218 female patients were included. The ovarian function was preserved in 125/132 (94.6%) of women who received GnRHa concurrently with CYC compared to 50/86 (58%) of women who did not receive GnRHa (OR = 10.3, CI = 4.83-36.29). The OR for pregnancy with GnRHa use = 2.94 (CI = 1.04-9.89). CONCLUSION Our results based on limited published studies suggest that concurrent GnRHa use preserves ovarian function and increase odds of pregnancy. It can be considered for premenopausal SLE females receiving CYC. Long-term follow-up studies are needed to establish the efficacy and safety of GnRHa use for ovarian preservation.
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Affiliation(s)
- Komal Ejaz
- The Wright Center for Graduate Medical Education, Scranton, Pennsylvania, USA
| | - Dania Abid
- Idaho College of Osteopathic Medicine, Meridian, Idaho, USA
| | - Paul Juneau
- National Institutes of Health Library, Bethesda, Maryland, USA,USA & Zimmerman Associates, Inc., Fairfax, Virginia, USA
| | - Jun Chu
- Lupus Clinical Trials Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Sarfaraz Hasni
- Lupus Clinical Trials Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA
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Giambalvo S, Garaffoni C, Silvagni E, Furini F, Rizzo R, Govoni M, Bortoluzzi A. Factors associated with fertility abnormalities in women with systemic lupus erythematosus: a systematic review and meta-analysis. Autoimmun Rev 2022; 21:103038. [PMID: 34995765 DOI: 10.1016/j.autrev.2022.103038] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Accepted: 01/01/2022] [Indexed: 11/28/2022]
Abstract
BACKGROUND Fertility is thought to be not affected in women with systemic lupus erythematosus (SLE), however disease-related factors, psychosocial effects of chronic disease, as well as medications exposure might impair gonadal function. OBJECTIVE This systematic literature review (SLR) aimed to explore clinical, hormonal, serological and treatment factors associated with fertility outcomes in women of childbearing age with SLE. METHODS This SLR was conducted following the Preferred Reporting Items for systematic reviews and Meta-analysis (PRISMA) statement. All articles available in English (1972 - 30th April 2021) in Pubmed, EMBASE, Scopus and Cochrane Library were screened. Study selection and data collection were performed by two independent reviewers. All data were extracted using a standardized template. The risk of bias of the included studies was assessed using the NIH risk-of-bias tool. RESULTS Of 789 abstracts evaluated, we included in this review 46 studies, of which 1 SLR, 16 cross-sectional studies, 18 cohort studies, 10 observational studies and 1 case-series, with data pertaining to 4704 patients (mean age 31.5 ± 3.7 years, disease duration 83.27 ± 38.3 months). Definitions of premature ovarian failure (POF) adopted in the studies varied in terms of the number of months of amenorrhea considered and the age of onset of amenorrhea. Clinical factors associated with the development of POF were older age at the time of initiation of therapy, and older age at the onset of SLE disease. Cyclophosphamide exposure (CYC) and its cumulative dose influenced gonadal function in SLE women, leading to amenorrhoea and POF, as reported in 19 studies. Mycophenolate, azathioprine, calcineurin inhibitors and steroids associated with a lower risk of POF compared to CYC. POF was less frequent in patients co-treated with CYC and gonadotropin-releasing hormone analogues (GnRH-a) compared with patients not receiving GnRH-a (risk ratio 0.798, 95%-CI [0.1417; 0.5525]). 11 studies evaluated the impact of damage accrual and disease activity on ovarian reserve with conflicting evidence. Finally, 18 studies investigated exposure to hormonal and serological factors and, among others, neither Anti-Müllerian Hormone nor anti-corpus luteum antibodies were associated with POF. CONCLUSION The strongest evidence regarding management factors associated with fertility in SLE women of childbearing age remains the treatment with CYC, as well as its cumulative dosage. Hormonal and serological factors appeared not to impact fertility outcomes, but they might be used as a surrogate of fertility, especially during the treatment with disease-specific drugs.
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Affiliation(s)
- S Giambalvo
- Unit of Rheumatology, Department of Medical Sciences, University of Ferrara, Azienda Ospedaliera-Universitaria Sant'Anna of Ferrara, Italy
| | - C Garaffoni
- Unit of Rheumatology, Department of Medical Sciences, University of Ferrara, Azienda Ospedaliera-Universitaria Sant'Anna of Ferrara, Italy
| | - E Silvagni
- Unit of Rheumatology, Department of Medical Sciences, University of Ferrara, Azienda Ospedaliera-Universitaria Sant'Anna of Ferrara, Italy
| | - F Furini
- Unit of Rheumatology, Ospedale Maggiore, Bologna, Italy
| | - R Rizzo
- Department of Chemical, Pharmaceutical and Agricultural Science, University of Ferrara, Italy
| | - M Govoni
- Unit of Rheumatology, Department of Medical Sciences, University of Ferrara, Azienda Ospedaliera-Universitaria Sant'Anna of Ferrara, Italy
| | - A Bortoluzzi
- Unit of Rheumatology, Department of Medical Sciences, University of Ferrara, Azienda Ospedaliera-Universitaria Sant'Anna of Ferrara, Italy.
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Ahmadian S, Sheshpari S, Pazhang M, Bedate AM, Beheshti R, Abbasi MM, Nouri M, Rahbarghazi R, Mahdipour M. Intra-ovarian injection of platelet-rich plasma into ovarian tissue promoted rejuvenation in the rat model of premature ovarian insufficiency and restored ovulation rate via angiogenesis modulation. Reprod Biol Endocrinol 2020; 18:78. [PMID: 32758249 PMCID: PMC7405361 DOI: 10.1186/s12958-020-00638-4] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2020] [Accepted: 07/29/2020] [Indexed: 02/07/2023] Open
Abstract
Premature Ovarian Insufficiency (POI) is viewed as a type of infertility in which the menopausal status occurs before the physiological age. Several therapeutic strategies have been introduced in clinic for POI treatment, although the outputs are not fully convincing. Platelet-rich plasma (PRP) is a unique blood product widely applied in regenerative medicine, which is based on the releasing of the growth factors present in platelets α-granules. In the current investigation, we examined the effectiveness of PRP as a therapeutic alternative for POI animals. POI in Wistar albino rats was induced by daily intraperitoneal (IP) administration of gonadotoxic chemical agent, 4-vinylcyclohexene dioxide (VCD) (160 mg/ kg) for 15 consecutive days. After POI induction, the PRP solution was directly injected intra-ovarian in two concentrations via a surgical intervention. Every two weeks post-injection, pathological changes were monitored in the ovaries using Hematoxylin-Eosin staining method, until eight weeks. Follicle Stimulating Hormone (FSH) content in serum was measured, together with the expression of the angiogenic-related transcripts ANGPT2 and KDR by real-time qPCR. Furthermore the fertility status of the treated rats was evaluated by mating trials. Histopathological examination revealed successful POI induction via the depletion of morphologically normal follicles in rats following VCD treatment compared to the control rats. The injection of PRP at two concentrations reduced the number and extent of the follicular atresia and inflammatory responses (p < 0.05). The expression of both ANGPT2 and KDR transcripts were significantly increased in POI rats due to enhanced inflammation, while these values were modulated after PRP administration (p < 0.05) compared to POI rats. FSH showed a decreased trend in concentration eight weeks after PRP treatment, but not statistically significant (p > 0.05). Nevertheless, a clear improvement in litter counts was found in POI rats receiving PRP compared to the non-treated POI group, being able to consider PRP as a facile, quick, accessible, safe and relatively cheap alternative therapeutic strategy to revert POI-related pathologies.
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Affiliation(s)
- Shahin Ahmadian
- Women's Reproductive Health Research Center, Tabriz University of Medical Sciences, Tabriz, 5138663134, Iran
- Department of Biology, Faculty of Basic Sciences, Azarbaijan Shahid Madani University, Tabriz, 537517169, Iran
| | - Sepideh Sheshpari
- Department of Midwifery, Faculty of Nursing and Midwifery, Tabriz University of Medical Sciences, Tabriz, 5138947977, Iran
| | - Mohammad Pazhang
- Department of Biology, Faculty of Basic Sciences, Azarbaijan Shahid Madani University, Tabriz, 537517169, Iran
| | - Alberto Miranda Bedate
- Laboratory for Translational Immunology (LTI), Universitair Medisch Centrum Utrecht, (UMCU), Utrecht, Heidelberglaan 100, 3584, CX, The Netherlands
| | - Rahim Beheshti
- Department of Veterinary Science, Islamic Azad University Shabestar Branch, Shabestar, 5381637181, Iran
| | | | - Mohammad Nouri
- Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, 5165665811, Iran
- Department of Reproductive Biology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, 5166653431, Iran
| | - Reza Rahbarghazi
- Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, 5165665811, Iran
- Department of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, 5166653431, Iran
| | - Mahdi Mahdipour
- Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, 5165665811, Iran.
- Department of Reproductive Biology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, 5166653431, Iran.
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Luong SN, Isaacs A, Liu Z, Sin FE, Giles I. A systematic review and meta-analysis of the gonadotoxic effects of cyclophosphamide and benefits of gonadotropin releasing hormone agonists (GnRHa) in women of child-bearing age with autoimmune rheumatic disease. Expert Rev Clin Immunol 2020; 16:321-333. [PMID: 32005081 DOI: 10.1080/1744666x.2020.1724091] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Objectives: To systematically review risk of sustained amenorrhea with intravenous (IV) cyclophosphamide in autoimmune rheumatic disease (ARD), and evaluate efficacy of gonadotropin-releasing hormone agonists (GnRHa) to reduce this risk.Methods: Systematic search for papers reporting incidence of sustained amenorrhea ≥12 months in ARD following: IV cyclophosphamide; or GnRHa and IV cyclophosphamide compared to IV cyclophosphamide alone.Results: From 31 articles and 1388 patients (mean age 27.7 years) sustained amenorrhea occurred in 273 patients (19.7%). Of 56 patients (mean age range 23.9-25.6 years) receiving GnRHa and IV cyclophosphamide, and 37 controls (mean age range 25-30.1 years) given IV cyclophosphamide only, sustained amenorrhea occurred in 2/56 (3.6%) patients treated with GnRHa, compared to 15/37 (40.5%) controls. Pooled odds ratio of sustained amenorrhea with GnRHa and cyclophosphamide versus cyclophosphamide alone was 0.054 (95% CI 0.0115-0.2576 p < 0.001), corresponding to a number needed to treat of 2.7 (95% CI 1.955-4.388) and absolute risk reduction of 36.95% (95% CI 35.6-38.4%).Conclusion: Sustained amenorrhea with IV cyclophosphamide was observed in patients with ARD, especially with increasing age and cumulative doses >5 g. GnRHa reduced this risk and should be considered with IV cyclophosphamide in women of childbearing age with ARD.
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Affiliation(s)
- Shi-Nan Luong
- Department of Rheumatology, University College London Hospital, London, UK.,Centre for Rheumatology, Division of Medicine, Rayne Institute, University College London, London, UK.,South Western Sydney Clinical School, Faculty of Medicine, University of New South Wales, Sydney, Australia
| | - Anthony Isaacs
- Department of Rheumatology, University College London Hospital, London, UK
| | - Zhixin Liu
- Stats Central, Mark Wainwright Analytical Centre, University of New South Wales, Sydney, Australia
| | - Fang E Sin
- Department of Rheumatology, University College London Hospital, London, UK
| | - Ian Giles
- Department of Rheumatology, University College London Hospital, London, UK.,Centre for Rheumatology, Division of Medicine, Rayne Institute, University College London, London, UK
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Liu H, Zhang Y, Li M, Luo P. Beneficial effect of Sepia esculenta ink polysaccharide on cyclophosphamide-induced immunosuppression and ovarian failure in mice. Int J Biol Macromol 2019; 140:1098-1105. [DOI: 10.1016/j.ijbiomac.2019.08.200] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2019] [Revised: 08/21/2019] [Accepted: 08/23/2019] [Indexed: 12/01/2022]
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Cui W, Stern C, Hickey M, Goldblatt F, Anazodo A, Stevenson WS, Phillips KA. Preventing ovarian failure associated with chemotherapy. Med J Aust 2019; 209:412-416. [PMID: 30376664 DOI: 10.5694/mja18.00190] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2018] [Accepted: 04/23/2018] [Indexed: 12/17/2022]
Abstract
Alkylating chemotherapy is often used to treat pre-menopausal women for various malignancies and autoimmune diseases. Chemotherapy-associated ovarian failure is a potential consequence of this treatment which can cause infertility, and increases the risk of other long term adverse health sequelae. Randomised trials, predominantly of women undergoing alkylating chemotherapy for breast cancer, have shown evidence for the efficacy of gonadotropin-releasing hormone agonists (GnRHa) in preventing chemotherapy-associated ovarian failure. The European St Gallen and United States National Comprehensive Cancer Network guidelines recommend the use of concurrent GnRHa to reduce the risk of ovarian failure for pre-menopausal women undergoing chemotherapy for breast cancer. The GnRHa goserelin, a monthly 3.6 mg depot subcutaneous injection, has recently been listed on the Australian Pharmaceutical Benefits Scheme to reduce risk of ovarian failure for pre-menopausal women receiving alkylating therapies for malignancy or autoimmune disease. The first dose of goserelin should ideally be administered at least 1 week before commencement of alkylating treatment and continued 4-weekly during chemotherapy. Concurrent goserelin use should now be considered for all pre-menopausal women due to commence alkylating chemotherapy (except those with incurable cancer), regardless of their childbearing status, in an effort to preserve their ovarian function. For women who have not completed childbearing, consideration of other fertility preservation options, such as cryopreservation of embryos or oocytes, is also important.
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Affiliation(s)
- Wanyuan Cui
- Peter MacCallum Cancer Centre, Melbourne, VIC
| | | | | | - Fiona Goldblatt
- Flinders Medical Centre and Flinders University, Adelaide, SA
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Yo JH, Barbour TD, Nicholls K. Management of refractory lupus nephritis: challenges and solutions. Open Access Rheumatol 2019; 11:179-188. [PMID: 31372070 PMCID: PMC6636187 DOI: 10.2147/oarrr.s166303] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2019] [Accepted: 05/13/2019] [Indexed: 12/15/2022] Open
Abstract
Refractory lupus nephritis, broadly defined as failure to attain clinical remission after appropriate induction immunosuppressive therapy, is associated with an increased risk of progression to end-stage kidney disease and mortality. This is a challenging issue in clinical practice, as modern induction therapy despite proven efficacy can still be associated with treatment failure. Moreover, newer therapies have failed in recent years to displace or even match existing protocols for effective induction of remission. Refractory disease is generally assessed on the basis of clinical parameters, which may be unreliable, and renal biopsy, which is often not performed in a standard or timely fashion. Persisting histological inflammation in 30%–50% of patients who have attained clinical remission highlights the disparity between clinical and immunological response to therapy. The lack of an international consensus regarding what constitutes refractory lupus nephritis compounds clinician indecision regarding optimal management for these patients. Moreover, non-adherence to prescribed therapy versus primary treatment failure can be challenging to discriminate, and the time point at which non-response becomes treatment failure is unclear. In this review, we assess the key published evidence for the treatment of refractory lupus nephritis and provide practical recommendations based around the use of adjunctive therapies. These agents include rituximab and calcineurin inhibitors, with evidence consisting largely of observational or uncontrolled studies, as well as some of the biologic therapies currently under investigation through prospective clinical trials. The poor prognosis of refractory lupus nephritis demands regular review of patient response and the flexibility to switch or augment therapy.
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Affiliation(s)
- J H Yo
- Department of Nephrology, The Royal Melbourne Hospital, Melbourne, Victoria, Australia
| | - T D Barbour
- Department of Nephrology, The Royal Melbourne Hospital, Melbourne, Victoria, Australia
| | - K Nicholls
- Department of Nephrology, The Royal Melbourne Hospital, Melbourne, Victoria, Australia
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10
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Vanni VS, De Lorenzo R, Privitera L, Canti V, Viganò P, Rovere-Querini P. Safety of fertility treatments in women with systemic autoimmune diseases (SADs). Expert Opin Drug Saf 2019; 18:841-852. [PMID: 31238745 DOI: 10.1080/14740338.2019.1636964] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
Introduction: Systemic Autoimmune Diseases (SADs) include systemic lupus erythematosus, antiphospholipid antibody syndrome, rheumatoid arthritis, systemic sclerosis, Sjogren's syndrome, mixed connective tissue disease, idiopathic inflammatory myopathies and vasculitis. SADs often occur in women of childbearing age and can affect fertility. Both infertility treatments and fertility preservation techniques are thus often indicated. Areas covered: The literature regarding the safety of fertility-related drugs for both fertility preservation and infertility treatment in patients affected by SADs was reviewed. Based on current knowledge, all the options for fertility preservation should be contemplated in patients with SADs who are at risk for fertility loss, including GnRH analogue administration, oocyte/embryo vitrification and ovarian tissue cryopreservation. Similarly, if pregnancy is not contraindicated in a patient with a SAD, neither should be any fertility treatment. Expert opinion: Women with SADs should postpone conception until a stable disease has been achieved for at least 6 months. When infertility treatments are needed, women with antiphospholipid antibodies should receive concomitant anticoagulation. If in vitro fertilization/intra-cytoplasmic sperm injection and embryo transfer is required, ovarian hyperstimulation and the inherent risk of thrombosis should be eliminated by GnRH-agonist trigger and cycle segmentation. Counselling about adherence to anti-rheumatic therapy to prevent disease exacerbations is also critical.
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Affiliation(s)
- V S Vanni
- a Reproductive Sciences Laboratory, Division of Genetics and Cell Biology, IRCCS San Raffaele Scientific Institute , Milan , Italy.,b Vita-Salute San Raffaele University , Milan , Italy
| | - R De Lorenzo
- b Vita-Salute San Raffaele University , Milan , Italy
| | - L Privitera
- c Division of Obstetrics and Gynecology, IRCCS San Raffaele Scientific Institute , Milan , Italy
| | - V Canti
- b Vita-Salute San Raffaele University , Milan , Italy
| | - P Viganò
- a Reproductive Sciences Laboratory, Division of Genetics and Cell Biology, IRCCS San Raffaele Scientific Institute , Milan , Italy
| | - P Rovere-Querini
- b Vita-Salute San Raffaele University , Milan , Italy.,d Division of Immunology, Transplantation & Infectious Diseases, IRCCS San Raffaele Scientific Institute , Milan , Italy
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Burgner A, Hladunewich MA. Women's Reproductive Health for the Nephrologist. Am J Kidney Dis 2019; 74:675-681. [PMID: 31221529 DOI: 10.1053/j.ajkd.2019.04.017] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2019] [Accepted: 04/05/2019] [Indexed: 02/08/2023]
Abstract
Women with chronic kidney disease (CKD) are faced with complex decisions and significant challenges during their reproductive years. Contraceptive choices have a variety of side effects that can disproportionately affect women with CKD, limiting choice. CKD itself and the therapies needed to treat severe disease can affect future fertility. When conception is desired, young women with CKD must plan meticulously because an ill-timed pregnancy can result in disease progression or flare and exposure of an unborn child to potentially teratogenic medications. Among women with CKD, pregnancy risks are substantial, with up to 10-fold higher risk for preeclampsia and 6-fold higher risk for preterm delivery. These pregnancy complications associated with inadequate placentation also increase maternal and newborn risks for cardiovascular morbidity and mortality and progression to kidney failure later in life. As such, it is the obligation of every nephrologist caring for women of reproductive age to provide guidance in the choice of methods to prevent unplanned pregnancies, to choose treatments that preserve fertility, and to participate in shared decision making that optimizes pregnancy timing and outcomes. In this perspective, we review the many challenges associated with reproductive counseling in women with CKD.
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Affiliation(s)
- Anna Burgner
- Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, TN
| | - Michelle A Hladunewich
- Division of Nephrology, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.
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12
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Condorelli M, Demeestere I. Challenges of fertility preservation in non-oncological diseases. Acta Obstet Gynecol Scand 2019; 98:638-646. [PMID: 30771251 DOI: 10.1111/aogs.13577] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2018] [Accepted: 02/11/2019] [Indexed: 12/15/2022]
Abstract
Clinicians should provide fertility counseling to all patients receiving gonadotoxic treatment. International scientific societies have mainly focused on oncological patients, and fewer efforts have been made to apply these recommendations to women diagnosed with benign disease (eg benign hematological diseases, autoimmune diseases, and gynecological or genetic disorders). However, these indications account for 8%-13% of the demand for fertility preservation. The risk of premature ovarian failure due to treatment, or to the disease itself, can be considered fairly high for many young women. Counseling and adequate management of these women require particular attention due to the severe health conditions that are associated with some of these diseases. In this review, we address specific issues related to providing adequate fertility counseling and management for women who have been diagnosed with the major non-oncological indications, based on the literature and on our clinical experience.
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Affiliation(s)
- Margherita Condorelli
- Research Laboratory on Human Reproduction and Fertility Clinic, CUB-Erasme, Université Libre de Bruxelles, Brussels, Belgium
| | - Isabelle Demeestere
- Research Laboratory on Human Reproduction and Fertility Clinic, CUB-Erasme, Université Libre de Bruxelles, Brussels, Belgium
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13
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Sofiyeva N, Siepmann T, Barlinn K, Seli E, Ata B. Gonadotropin-Releasing Hormone Analogs for Gonadal Protection During Gonadotoxic Chemotherapy: A Systematic Review and Meta-Analysis. Reprod Sci 2018; 26:939-953. [PMID: 30270741 DOI: 10.1177/1933719118799203] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
OBJECTIVE A systematic review and meta-analysis was conducted to investigate whether gonadotropin-releasing hormone analogs (GnRHa) have a protective role in women treated with alkylating agents. DATA SOURCES Major databases (PubMED, EMBASE, Cochrane Central Register of Controlled Trials), systematic snowballing, and trial registries were screened from the inception dates until September 2017. METHODS AND STUDY SELECTION Comparative studies involving reproductive-aged women undergoing chemotherapy with or without coadministration of GnRHa were included. Spontaneous menstrual resumption was assessed as a main outcome. Statistical analyses were performed with STATA 14.2 statistical software. Effect estimates were presented as risk ratios (RR) with 95% confidence intervals (CIs). RESULTS The literature search yielded 25 436 citations and 84 papers were assessed in full text. Eighteen studies (11 randomized controlled trials [RCTs] and 7 cohort studies) published between 1987 and 2015 were included in the analysis, revealing a significant protective effect of GnRHa (n = 1043; RR:1.38; 95% CI: 1.18-1.63) although with high heterogeneity (I2 = 83.3%). Subgroup analyses revealed a significant benefit of GnRHa cotreatment both in RCTs and in cohort studies. Statistical significance was found in all subgroups by the underlying disease, that is, hematological malignancies, autoimmune diseases, and breast cancer. Sensitivity analyses in GnRH agonist-treated patients, in patients younger than 40 years old, and in patients without supradiaphragmatic radiotherapy also revealed a significant benefit of GnRHa cotreatment. CONCLUSION Our results indicate that concurrent GnRHa administration is an effective method to decrease gonadotoxicity of alkylating agents. The presence of low-quality evidence favoring gonadoprotective effect requires a strong recommendation for offering GnRHa coadministration to young women who are to undergo gonadotoxic chemotherapy. CAPSULE The present systematic review and meta-analysis shows a significant gonadoprotective effect of gonadotropin-releasing hormone analogs in women treated with alkylating agents.
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Affiliation(s)
- Nigar Sofiyeva
- 1 Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University, School of Medicine, New Haven, CT, USA.,2 Division of Health Care Sciences, Center for Clinical Research and Management Education, Dresden International University, Dresden, Germany
| | - Timo Siepmann
- 2 Division of Health Care Sciences, Center for Clinical Research and Management Education, Dresden International University, Dresden, Germany.,3 Department of Neurology, University Hospital Carl Gustav Carus, Technische Universitaet Dresden, Dresden, Germany
| | - Kristian Barlinn
- 3 Department of Neurology, University Hospital Carl Gustav Carus, Technische Universitaet Dresden, Dresden, Germany
| | - Emre Seli
- 1 Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University, School of Medicine, New Haven, CT, USA
| | - Baris Ata
- 1 Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University, School of Medicine, New Haven, CT, USA.,4 Department of Obstetrics and Gynecology, Koc University, School of Medicine, Istanbul, Turkey
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Koga T, Umeda M, Endo Y, Ishida M, Fujita Y, Tsuji S, Takatani A, Shimizu T, Sumiyoshi R, Igawa T, Fukui S, Nishino A, Kawashiri SY, Iwamoto N, Ichinose K, Tamai M, Nakamura H, Origuchi T, Murakami N, Kitajima M, Kawakami A. Effect of a gonadotropin-releasing hormone analog for ovarian function preservation after intravenous cyclophosphamide therapy in systemic lupus erythematosus patients: a retrospective inception cohort study. Int J Rheum Dis 2018; 21:1287-1292. [DOI: 10.1111/1756-185x.13318] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Affiliation(s)
- Tomohiro Koga
- Division of Advanced Preventive Medical Sciences; Department of Immunology and Rheumatology; Nagasaki University Graduate School of Biomedical Sciences; Nagasaki Japan
- Center for Bioinformatics and Molecular Medicine; Nagasaki University Graduate School of Biomedical Sciences; Nagasaki Japan
| | - Masataka Umeda
- Division of Advanced Preventive Medical Sciences; Department of Immunology and Rheumatology; Nagasaki University Graduate School of Biomedical Sciences; Nagasaki Japan
- Medical Education Development Center; Nagasaki University Hospital; Nagasaki Japan
| | - Yushiro Endo
- Division of Advanced Preventive Medical Sciences; Department of Immunology and Rheumatology; Nagasaki University Graduate School of Biomedical Sciences; Nagasaki Japan
| | - Midori Ishida
- Division of Advanced Preventive Medical Sciences; Department of Immunology and Rheumatology; Nagasaki University Graduate School of Biomedical Sciences; Nagasaki Japan
| | - Yuya Fujita
- Division of Advanced Preventive Medical Sciences; Department of Immunology and Rheumatology; Nagasaki University Graduate School of Biomedical Sciences; Nagasaki Japan
| | - Sosuke Tsuji
- Division of Advanced Preventive Medical Sciences; Department of Immunology and Rheumatology; Nagasaki University Graduate School of Biomedical Sciences; Nagasaki Japan
| | - Ayuko Takatani
- Division of Advanced Preventive Medical Sciences; Department of Immunology and Rheumatology; Nagasaki University Graduate School of Biomedical Sciences; Nagasaki Japan
| | - Toshimasa Shimizu
- Division of Advanced Preventive Medical Sciences; Department of Immunology and Rheumatology; Nagasaki University Graduate School of Biomedical Sciences; Nagasaki Japan
| | - Remi Sumiyoshi
- Division of Advanced Preventive Medical Sciences; Department of Immunology and Rheumatology; Nagasaki University Graduate School of Biomedical Sciences; Nagasaki Japan
| | - Takashi Igawa
- Division of Advanced Preventive Medical Sciences; Department of Immunology and Rheumatology; Nagasaki University Graduate School of Biomedical Sciences; Nagasaki Japan
| | - Shoichi Fukui
- Division of Advanced Preventive Medical Sciences; Department of Immunology and Rheumatology; Nagasaki University Graduate School of Biomedical Sciences; Nagasaki Japan
- Unit of Advanced Preventive Medical Sciences; Department of Community Medicine; Nagasaki University Graduate School of Biomedical Sciences; Nagasaki Japan
| | - Ayako Nishino
- Division of Advanced Preventive Medical Sciences; Department of Immunology and Rheumatology; Nagasaki University Graduate School of Biomedical Sciences; Nagasaki Japan
- Center for Comprehensive Community Care Education; Nagasaki University Graduate School of Biomedical Sciences; Nagasaki Japan
| | - Shin-ya Kawashiri
- Division of Advanced Preventive Medical Sciences; Department of Immunology and Rheumatology; Nagasaki University Graduate School of Biomedical Sciences; Nagasaki Japan
- Unit of Advanced Preventive Medical Sciences; Department of Community Medicine; Nagasaki University Graduate School of Biomedical Sciences; Nagasaki Japan
| | - Naoki Iwamoto
- Division of Advanced Preventive Medical Sciences; Department of Immunology and Rheumatology; Nagasaki University Graduate School of Biomedical Sciences; Nagasaki Japan
| | - Kunihiro Ichinose
- Division of Advanced Preventive Medical Sciences; Department of Immunology and Rheumatology; Nagasaki University Graduate School of Biomedical Sciences; Nagasaki Japan
| | - Mami Tamai
- Division of Advanced Preventive Medical Sciences; Department of Immunology and Rheumatology; Nagasaki University Graduate School of Biomedical Sciences; Nagasaki Japan
| | - Hideki Nakamura
- Division of Advanced Preventive Medical Sciences; Department of Immunology and Rheumatology; Nagasaki University Graduate School of Biomedical Sciences; Nagasaki Japan
| | - Tomoki Origuchi
- Division of Advanced Preventive Medical Sciences; Department of Immunology and Rheumatology; Nagasaki University Graduate School of Biomedical Sciences; Nagasaki Japan
| | - Naoko Murakami
- Department of Obstetrics and Gynecology; Nagasaki University Graduate School of Biomedical Sciences; Nagasaki Japan
| | - Michio Kitajima
- Department of Obstetrics and Gynecology; Nagasaki University Graduate School of Biomedical Sciences; Nagasaki Japan
| | - Atsushi Kawakami
- Division of Advanced Preventive Medical Sciences; Department of Immunology and Rheumatology; Nagasaki University Graduate School of Biomedical Sciences; Nagasaki Japan
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15
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Schüring AN, Fehm T, Behringer K, Goeckenjan M, Wimberger P, Henes M, Henes J, Fey MF, von Wolff M. Practical recommendations for fertility preservation in women by the FertiPROTEKT network. Part I: Indications for fertility preservation. Arch Gynecol Obstet 2017; 297:241-255. [PMID: 29177593 PMCID: PMC5762797 DOI: 10.1007/s00404-017-4594-3] [Citation(s) in RCA: 68] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2017] [Accepted: 11/10/2017] [Indexed: 12/11/2022]
Abstract
Purpose Most guidelines about fertility preservation are predominantly focused on scientific evidence, but are less practically orientated. Therefore, practically oriented recommendations are needed to support the clinician in daily practice. Methods A selective literature search was performed based on the clinical and scientific experience of the authors, focussing on the most relevant diseases and gynaecological cancers. This article (Part I) provides information on topics that are essential for the fertility preservation indication, such as disease prognosis, disease therapy and its associated risks to fertility, recommending disease-specific fertility preservation measures. Part II specifically focusses on fertility preservation techniques. Results In breast cancer patients, fertility preservation such as ovarian tissue and oocyte cryopreservation is especially recommended in low-stage cancer and in women < 35 years of age. In Hodgkin’s lymphoma, the indication is mainly based on the chemotherapy regime as some therapies have very low, others very high gonadotoxicity. In borderline ovarian tumours, preservation of fertility usually is achieved through fertility sparing surgery, ovarian stimulation may also be considered. In cervical cancer, endometrial cancer, rheumatic diseases and other malignancies such as Ewing sarcoma, colorectal carcinoma, non-Hodgkin lymphoma, leukaemia etc., several other factors must be considered to enable an individual, stage-dependent decision. Conclusion The decision for or against fertility preservation depends on the prognosis, the risks to fertility and individual factors such as prospective family planning.
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Affiliation(s)
- A N Schüring
- UKM Kinderwunschzentrum, Department of Gynaecology and Obstetrics, University Hospital of Münster, Albert-Schweitzer Campus 1, D-11, 48149, Münster, Germany.
| | - T Fehm
- Department of Gynaecology and Obstetrics, University Hospital of Düsseldorf, Düsseldorf, Germany
| | - K Behringer
- Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany
| | - M Goeckenjan
- Department of Gynaecology and Obstetrics, TU Dresden, Dresden, Germany
| | - P Wimberger
- Department of Gynaecology and Obstetrics, TU Dresden, Dresden, Germany
| | - M Henes
- Department of Women's Health, University of Tübingen, Tübingen, Germany
| | - J Henes
- Centre for Interdisciplinary Clinical Immunology, Rheumatology and Auto-inflammatory Diseases and Department of Internal Medicine II (Oncology, Hematology, Immunology, Rheumatology, Pulmology), University of Tübingen, Tübingen, Germany
| | - M F Fey
- Department of Medical Oncology, Inselspital and University of Berne, Berne, Switzerland
| | - M von Wolff
- Division of Gynaecological Endocrinology and Reproductive Medicine, University Women's Hospital, Berne, Switzerland
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16
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Imai A, Ichigo S, Matsunami K, Takagi H, Kawabata I. Ovarian function following targeted anti-angiogenic therapy with bevacizumab. Mol Clin Oncol 2017; 6:807-810. [PMID: 28588768 DOI: 10.3892/mco.2017.1237] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2016] [Accepted: 04/04/2017] [Indexed: 01/12/2023] Open
Abstract
Improvements in cancer therapy have enabled further insight into the long-term effects of treatment, including the highly prevalent gonadal failure. The focus of treatment has been shifted to the preservation of fertility, which may be achieved by preventing ovarian toxicity. To this end, new molecular-targeted agents, including monoclonal antibodies, have been developed and used in a standard procedure for managing different cancers. However, the prolonged antitumor activity of these drugs may cause the emergence of new toxic effects. The aim of the present review was to discuss the leading toxic effect of the anti-angiogenic agent bevacizumab on ovarian function in female patients of reproductive age, which may be observed and expected during in clinical practice. The majority of bevacizumab-induced side effects are expected to be transient and eliminated within the anticipated drug clearance time frame; however, fundamental investigations on these effects are required for generating more evidence-based practice guidelines.
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Affiliation(s)
- Atsushi Imai
- Department of Obstetrics and Gynecology, Matsunami General Hospital, Kasamatsu, Gifu 501-6062, Japan
| | - Satoshi Ichigo
- Department of Obstetrics and Gynecology, Matsunami General Hospital, Kasamatsu, Gifu 501-6062, Japan
| | - Kazutoshi Matsunami
- Department of Obstetrics and Gynecology, Matsunami General Hospital, Kasamatsu, Gifu 501-6062, Japan
| | - Hiroshi Takagi
- Department of Obstetrics and Gynecology, Matsunami General Hospital, Kasamatsu, Gifu 501-6062, Japan
| | - Ichiro Kawabata
- Department of Obstetrics and Gynecology, Matsunami General Hospital, Kasamatsu, Gifu 501-6062, Japan
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17
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Zhou X, He W, Zhu R, Zheng Y. Impact of GnRHa pretreatment on the autotransplatation efficacy of cytopreserved rat ovarian tissue. Biomed Pharmacother 2016; 86:136-142. [PMID: 27960135 DOI: 10.1016/j.biopha.2016.11.070] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2016] [Revised: 11/12/2016] [Accepted: 11/16/2016] [Indexed: 11/28/2022] Open
Abstract
Pre-therapeutic cryopreservation of ovarian tissue and subsequent transplantation after disease remission has recently emerged as an option to restore endocrinal function and preserve fertility for patients subjected to gonadotoxic treatments such as chemotherapy. However, the relatively low survival rate of follicles after grafting the frozen-thawed ovarian tissue largely limited the application of this technique. Gonadotropin-releasing hormone analogues (GnRHa), owing to their endocrinal regulatory effect, have been successfully used for fertility preservation against gonadotoxic conditions such as cytotoxic agents based anti-cancer therapy. In this study, we evaluated the potential protective effect of precedent GnRHa treatment before cryopreservation on freezing-thawing related follicular damages using a rat autoxenograft model. We have observed that GnRHa significantly increases the fraction of follicles with normal morphology, while presenting negnigible effect on the physiological recovery of the grafted follicular tissue, as demonstrated by the estrous cycle, folliculogenesis and post-autograft vascularization. Our data implicates that GnRHa pretreatment may effectively increase the efficacy of cryopreservation and the subsequent successful rate of transplantation.
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Affiliation(s)
- Xinhui Zhou
- Department of Gynecology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, China
| | - Weihua He
- Department of Gynecology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, China
| | - Rong Zhu
- Department of Gynecology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, China
| | - Yulong Zheng
- Department of Medical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, China.
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18
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Silva CAA, Brunner HI. Review: Gonadal functioning and preservation of reproductive fitness with juvenile systemic lupus erythematosus. Lupus 2016; 16:593-9. [PMID: 17711894 DOI: 10.1177/0961203307077538] [Citation(s) in RCA: 61] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Increased survival of children with juvenile systemic lupus erythematosus (jSLE) and improved prognosis have led to a change in the long-term health issues arising for jSLE patients. Preservation of gonadal functioning and fertility are of increasing importance for young adults with jSLE. Events during childhood, such as exposure to alkylating agents, may compromise the reproductive potential. Even in the absence of gonadotoxic therapies, fertility may be decreased through organs specific involvement with jSLE. Strategies to preserve the reproductive potential of girl and boys with jSLE are discussed. Lupus (2007) 16, 593—599.
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Affiliation(s)
- C A A Silva
- Pediatric Rheumatology Unit, Children's Hospital, and Division of Rheumatology of University of São Paulo, São Paulo, Brazil
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19
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Abstract
Although not licensed for systemic lupus erythematosus (SLE), cyclophosphamide (CYC) has become over the last two decades the most widely prescribed cytotoxic drug for lupus nephritis (LN). A PubMed search using ‘lupus nephritis and cyclophosphamide’ as key words identifies not less than 454 papers on the topic. This should, however, not disguise the fact that its use is still controversial and that many issues remain debated, such as the timing and length of treatment, the route of administration and the ideal dosage. In this review, the different CYC regimes on the basis of the results of prospective randomized trials performed in LN patients is discussed.
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Affiliation(s)
- F A Houssiau
- Rheumatology Department, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Bruxelles, Belgium.
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20
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Tincani A, Nuzzo M, Lojacono A, Cattalini M, Meini A. Review: Contraception in adolescents with systemic lupus erythematosus. Lupus 2016; 16:600-5. [PMID: 17711895 DOI: 10.1177/0961203307078074] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
In the management of adolescents with systemic lupus erythematosus (SLE), sexual activity and prevention of unwanted pregnancies are important topics. Many contraceptive methods are available nowadays. Oral contraceptives (OCs) are the preferred choice among adolescents in general. However, the use of these medications in adolescents with SLE raises serious concerns, particularly the risk of thrombotic events from estrogen exposure and the impact of these medications on lupus activity. In this article, different contraceptive methods available are reviewed and their application in adolescents with SLE is discussed. In conclusion, OCs are the methods of choice in adolescents with stable disease and no antiphospholipid antibodies (aPL) detected. In patients with aPL, fewer options are available, and the selection of the preferred form of contraception should be made on an individual basis. Lupus (2007) 16, 600—605.
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Affiliation(s)
- A Tincani
- Department of Rheumatology and Clinical Immunology, Brescia Hospital and University of Brescia, Brescia, Italy.
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21
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Abstract
Systemic lupus erythematosus (SLE) is a rare, severe, multisystem autoimmune disorder. Childhood-onset SLE (cSLE) follows a more aggressive course with greater associated morbidity and mortality than adult-onset SLE. Its aetiology is yet to be fully elucidated. It is recognised to be the archetypal systemic autoimmune disease, arising from a complex interaction between the innate and adaptive immune systems. Its complexity is reflected by the fact that there has been only one new drug licensed for use in SLE in the last 50 years. However, biologic agents that specifically target aspects of the immune system are emerging. Immunosuppression remains the cornerstone of medical management, with glucocorticoids still playing a leading role. Treatment choices are led by disease severity. Immunosuppressants, including azathioprine and methotrexate, are used in mild to moderate manifestations. Mycophenolate mofetil is widely used for lupus nephritis. Cyclophosphamide remains the first-line treatment for patients with severe organ disease. No biologic therapies have yet been approved for cSLE, although they are being used increasingly as part of routine care of patients with severe lupus nephritis or with neurological and/or haematological involvement. Drugs influencing B cell survival, including belimumab and rituximab, are currently undergoing clinical trials in cSLE. Hydroxychloroquine is indicated for disease manifestations of all severities and can be used as monotherapy in mild disease. However, the management of cSLE is hampered by the lack of a robust evidence base. To date, it has been principally guided by best-practice guidelines, retrospective case series and adapted adult protocols. In this pharmacological review, we provide an overview of current practice for the management of cSLE, together with recent advances in new therapies, including biologic agents.
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22
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Lee PA, Houk CP. Gonadotropin-releasing hormone analog therapy for central precocious puberty and other childhood disorders affecting growth and puberty. ACTA ACUST UNITED AC 2016; 5:287-96. [PMID: 17002488 DOI: 10.2165/00024677-200605050-00003] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022]
Abstract
Gonadotropin-releasing hormone (GnRH) analog therapy relies primarily on the ability of these compounds to bind to and modulate GnRH-receptor activity. GnRH analogs have been used in pediatric patients where endogenous gonadotropin release is undesirable or potentially harmful, such as in: (i) patients with central precocious puberty (CPP); (ii) healthy short children where pubertal delay would provide an opportunity to supplement pre-pubertal linear growth; and (iii) children with malignancies and other disorders where treatment requires the use of gonadotoxic compounds. In the first two groups of patients, GnRH agonists may be used alone or in conjunction with somatropin (growth hormone [GH]) to prevent early skeletal maturation and increase the subsequent adult height, while in the latter case, GnRH agonists are used alone or in conjunction with GnRH antagonists in an attempt to preserve gonadal function.In children and adolescents with CPP, timely use of GnRH agonists alone can result in an adult height within the genetic potential of the individual (target height); however, minimal height is gained when GnRH agonist therapy is commenced after a marked advancement of skeletal age. This provides the rationale for combined therapy with GnRH agonists and somatropin in such patients, and studies have shown improved growth with this approach compared with GnRH agonists alone. Combination therapy with GnRH agonists and somatropin has also been shown to increase adult heights to a greater extent than GnRH agonists alone in pediatric patients with concomitant CPP and GH deficiency, those with idiopathic short stature, and those born small for gestational age; however, such combination therapy has shown no increased benefit over somatropin alone in pediatric patients with GH deficiency. Limited results in children and adolescents with congenital adrenal hyperplasia and chronic primary hypothyroidism have also shown increased growth rates, while no growth benefit was seen in pediatric renal transplant recipients.GnRH analogs also have potential as gonadoprotective agents; studies of GnRH agonists used alone and in combination with GnRH antagonists in women undergoing cytotoxic therapy have shown increased preservation of reproductive potential in patients who were receiving GnRH analog therapy versus those who were not.The adverse effects of GnRH analogs mainly consist of menopausal-like complaints. Increases in bodyweight and body mass index in children receiving GnRH agonist therapy have been shown; however, these increases do not persist after discontinuation of therapy. Adult bone mineral density and fertility are also not adversely affected by childhood GnRH agonist therapy.GnRH analog therapy appears to be both well tolerated and effective in pediatric patients, as it allows the preservation or improvement of adult height, and shows no longstanding negative effects on body composition, bone density, reproductive function, or endocrine physiology. These agents may also be useful for preservation of gonadal function in children and adolescents undergoing cytotoxic therapy.
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Affiliation(s)
- Peter A Lee
- Department of Pediatrics, Penn State College of Medicine, The Milton S. Hershey Medical Center, Hershey, Pennsylvania, USA
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Knickelbein JE, Armbrust KR, Kim M, Sen HN, Nussenblatt RB. Pharmacologic Treatment of Noninfectious Uveitis. Handb Exp Pharmacol 2016; 242:231-268. [PMID: 27848029 DOI: 10.1007/164_2016_21] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Uveitis encompasses a spectrum of diseases whose common feature is intraocular inflammation, which may be infectious or noninfectious in etiology (Nussenblatt and Whitcup 2010). Infectious causes of uveitis are typically treated with appropriate antimicrobial therapy and will not be discussed in this chapter. Noninfectious uveitides are thought have an autoimmune component to their etiology and are thus treated with anti-inflammatory agents.
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Affiliation(s)
- Jared E Knickelbein
- Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bldg 10 Room 10N109, 10 Center Drive, Bethesda, MD, 20892, USA
| | - Karen R Armbrust
- Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bldg 10 Room 10N109, 10 Center Drive, Bethesda, MD, 20892, USA
| | - Meredith Kim
- Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bldg 10 Room 10N109, 10 Center Drive, Bethesda, MD, 20892, USA
| | - H Nida Sen
- Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bldg 10 Room 10N109, 10 Center Drive, Bethesda, MD, 20892, USA
| | - Robert B Nussenblatt
- Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bldg 10 Room 10N109, 10 Center Drive, Bethesda, MD, 20892, USA.
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24
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Marder W, Vinet É, Somers EC. Rheumatic autoimmune diseases in women and midlife health. Womens Midlife Health 2015; 1:11. [PMID: 28553545 PMCID: PMC5444314 DOI: 10.1186/s40695-015-0012-9] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2015] [Accepted: 11/03/2015] [Indexed: 01/03/2023] Open
Abstract
Autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and systemic sclerosis (scleroderma) preferentially affect women, and are characterized by systemic inflammation leading to target organ dysfunction. The public health burden of autoimmune diseases, which collectively represent a leading cause of morbidity and mortality among women throughout adulthood, is substantial. While some features of these diseases have been observed to improve over the menopausal transition, such as disease flare rate in SLE and skin softening and thinning in scleroderma, others, such as swollen and tender joints and radiographically confirmed damage in RA may worsen. The general trends, however, are not consistent or conclusive for all disease-related manifestations. Of great importance is the recognition that comorbid diseases, including osteoporosis and accelerated cardiovascular disease, contribute excess morbidity and mortality that becomes increasingly apparent as women with autoimmune diseases undergo the menopausal transition.
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Affiliation(s)
- Wendy Marder
- Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI USA
- Department of Obstetrics & Gynecology, University of Michigan, Ann Arbor, MI USA
| | - Évelyne Vinet
- Division of Rheumatology, McGill University Health Centre, Montreal, Canada
- Division of Clinical Epidemiology, McGill University Health Centre, Montreal, Canada
| | - Emily C. Somers
- Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI USA
- Department of Obstetrics & Gynecology, University of Michigan, Ann Arbor, MI USA
- Department of Environmental Health Sciences, University of Michigan, 2800 Plymouth Rd, NCRC B14-G236, Ann Arbor, MI 48109-2800 USA
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Li Z, Mewawalla P, Stratton P, Yong ASM, Shaw BE, Hashmi S, Jagasia M, Mohty M, Majhail NS, Savani BN, Rovó A. Sexual health in hematopoietic stem cell transplant recipients. Cancer 2015; 121:4124-31. [PMID: 26372459 DOI: 10.1002/cncr.29675] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2015] [Revised: 08/02/2015] [Accepted: 08/10/2015] [Indexed: 01/22/2023]
Abstract
Hematopoietic stem cell transplantation (HSCT) plays a central role in patients with malignant and, increasingly, nonmalignant conditions. As the number of transplants increases and the survival rate improves, long-term complications are important to recognize and treat to maintain quality of life. Sexual dysfunction is a commonly described but relatively often underestimated complication after HSCT. Conditioning regimens, generalized or genital graft-versus-host disease, medications, and cardiovascular complications as well as psychosocial problems are known to contribute significantly to physical and psychological sexual dysfunction. Moreover, it is often a difficult topic for patients, their significant others, and health care providers to discuss. Early recognition and management of sexual dysfunction after HSCT can lead to improved quality of life and outcomes for patients and their partners. This review focuses on the risk factors for and treatment of sexual dysfunction after transplantation and provides guidance concerning how to approach and manage a patient with sexual dysfunction after HSCT.
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Affiliation(s)
- Zhuoyan Li
- Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Prerna Mewawalla
- Department of Hematology, Western Pennsylvania Cancer Institute, Pittsburgh, Pennsylvania
| | - Pamela Stratton
- Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland
| | - Agnes S M Yong
- Department of Haematology, SA Pathology, and School of Medicine, University of Adelaide, Adelaide, South Australia, Australia
| | - Bronwen E Shaw
- Center for International Blood and Marrow Transplant Research, Froedtert and the Medical College of Wisconsin, Milwaukee, Wisconsin
| | | | - Madan Jagasia
- Hematology and Stem Cell Transplantation Section, Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center and Veterans Affairs Medical Center, Nashville, Tennessee
| | - Mohamad Mohty
- INSERM (National Institute of Health and Medical Research) 938, Paris, France
| | - Navneet S Majhail
- Blood and Marrow Transplant Program, Cleveland Clinic, Cleveland, Ohio
| | - Bipin N Savani
- Hematology and Stem Cell Transplantation Section, Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center and Veterans Affairs Medical Center, Nashville, Tennessee
| | - Alicia Rovó
- Department of Hematology, University Hospital of Bern, Bern, Switzerland
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Gajjar R, Miller SD, Meyers KE, Ginsberg JP. Fertility preservation in patients receiving cyclophosphamide therapy for renal disease. Pediatr Nephrol 2015; 30:1099-106. [PMID: 25190492 DOI: 10.1007/s00467-014-2897-1] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2014] [Revised: 05/21/2014] [Accepted: 06/24/2014] [Indexed: 12/15/2022]
Abstract
Cyclophosphamide continues to have an important role in the treatment of renal disease, including nephrotic syndrome and lupus nephritis, despite known complications of gonadotoxicity and potential infertility in both male and female patients. It is important that the physician recommending this therapy mitigates the effect of the drug on fertility by adhering to recommendations on dosing limits and offering fertility-preserving strategies. In addition to well-established methods, such as sperm banking and embryo cryopreservation, advances in reproductive technology have yielded strategies such as oocyte cryopreservation, resulting in more fertility-preserving options for the pediatric patient. Despite these advances, there continues to be a significant barrier to referral and access to sperm banks and fertility specialists. These issues are further complicated by ethical issues associated with the treatment of pediatric patients. In this review we explore the development of recommended dosing limits and include a discussion of the available fertility-preserving methods, strategies for increasing access to fertility specialists, and the ethical considerations facing the pediatric healthcare provider.
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Affiliation(s)
- Radha Gajjar
- Division of Nephrology, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA,
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Brunner HI, Silva CA, Reiff A, Higgins GC, Imundo L, Williams CB, Wallace CA, Aikawa NE, Nelson S, Klein-Gitelman MS, Rose SR. Randomized, double-blind, dose-escalation trial of triptorelin for ovary protection in childhood-onset systemic lupus erythematosus. Arthritis Rheumatol 2015; 67:1377-85. [PMID: 25676588 DOI: 10.1002/art.39024] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2014] [Accepted: 01/06/2015] [Indexed: 02/04/2023]
Abstract
OBJECTIVE To determine the dose of triptorelin that is sufficient to maintain complete ovarian suppression in female patients with childhood-onset systemic lupus erythematosus (SLE) who require cyclophosphamide therapy, to determine the length of time needed to achieve ovarian suppression after initiation of triptorelin treatment, and to investigate the safety of triptorelin. METHODS In this randomized, double-blind, placebo-controlled, dose-escalation study, female patients ages <21 years were randomized 4:1 to receive triptorelin (n = 25) or placebo (n = 6). The starting doses of triptorelin were 25, 50, 75, and 100 μg/kg, and the dose was escalated until complete ovarian suppression was maintained. The primary outcome was the weight-adjusted dose of triptorelin that provided complete ovarian suppression in at least 90% of the patients, as determined by gonadotropin-releasing hormone agonist stimulation testing. The secondary outcome was the period of time required to achieve ovarian suppression, as measured by unstimulated follicle-stimulating hormone and luteinizing hormone levels after the initiation of triptorelin treatment. RESULTS Treatment with triptorelin at a weight-adjusted dose of 120 μg/kg body weight provided sustained complete ovarian suppression in 90% of the patients. After administration of the initial dose of triptorelin, 22 days were required to achieve complete ovarian suppression. The rates of adverse events (AEs) and serious adverse events (SAEs) per 100 patient-months of followup were not higher in the triptorelin group compared with the placebo group (for AEs, 189 versus 362; for SAEs, 2.1 versus 8.5). CONCLUSION High doses of triptorelin are needed to achieve and maintain complete ovarian suppression, but such doses appear to be well tolerated in adolescent female patients with childhood-onset SLE. Our data suggest that a lag time of 22 days after initiation of triptorelin treatment is required before cyclophosphamide therapy is started or continued.
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Affiliation(s)
- Hermine I Brunner
- Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio
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Peracha J, Morgan MD. Urological manifestations and treatment of the primary systemic vasculitides. World J Clin Urol 2015; 4:5-20. [DOI: 10.5410/wjcu.v4.i1.5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2014] [Revised: 11/17/2014] [Accepted: 12/31/2014] [Indexed: 02/06/2023] Open
Abstract
The primary systemic vasculitides (PSV) are a group of rare inflammatory disorders affecting blood vessels of varying size and multiple organs. Urological manifestations of PSV are uncommon. Testicular vasculitis is the most commonly reported finding and is associated with Polyarteritis Nodosa (PAN), Henoch-Schönlein Purpura (HSP), anti-neutrophil cytoplasm antibody associated Vasculitides (AAV), Giant Cell Arteritis (GCA) and Kawasaki disease. Prostatic vasculitis has been reported in association with GCA and AAV. Ureteric involvement has been noted in PAN, HSP and AAV. Other urogenital manifestations of PSV include genital ulceration and bladder dysfunction in Behçets Disease and haematuria which is commonly seen in many of the PSV. Finally, therapies used to treat the PSV, especially cyclophosphamide, are associated with urological side-effects including haemorrhagic cystitis and urothelial malignancy. The aim of this review is to examine how the urological system is involved in the PSV. Each PSV is examined in turn, with a brief clinical description of the disease followed by a description of the urological manifestations and management. Identification of urological manifestations of PSV is important as in many cases symptoms may improve with immunosuppressive therapy, avoiding the need for invasive surgery. Additionally, patients who present with isolated urogenital PSV are at higher risk of developing subsequent systemic vasculitis and will need to be followed up closely.
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Risks associated with premature ovarian failure in Han Chinese women. Reprod Biomed Online 2015; 30:401-7. [PMID: 25682306 DOI: 10.1016/j.rbmo.2014.12.013] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2014] [Revised: 12/17/2014] [Accepted: 12/17/2014] [Indexed: 01/09/2023]
Abstract
In this retrospective study, the relationship between demographic characteristics, past medical history, general lifestyle habits and susceptibility of premature ovarian failure (POF) in Han Chinese population was investigated. Five hundred and fifty-three patients with POF and 400 women with normal ovarian function were recruited. A questionnaire was designed to gather information from responders. Logistic regression was carried out to calculate odds ratios (OR), 95% confidence intervals (95% CI) and P-values. History of pelvic surgery, mumps, having relatives with menstrual abnormalities and exposure to chemical agents were significantly associated with increased risk of POF (OR 5.53 [2.15 to 14.23]; 3.26 [2.38 to 4.47]; 28.12 [8.84 to 89.46]; 4.47 [2.09 to 9.58]). Vegetarian diet, tea and mineral water consumption reduced the risk of POF (OR 0.27 [0.19 to 0.37]; 0.04 [0.03 to 0.07]; 0.63 [0.47 to 0.85], respectively). Heredity, pelvic surgery, mumps and exposure to chemical agents were identified as risk factors for POF, whereas vegetarian diet, tea consumption and mineral water drinking were protective. Therefore, genetic consultation could help those women whose relatives manifested an early or premature menopause to avoid the consequences of possible premature ovarian function cessation. Avoidance of exposure to endocrine disrupters and flavonoids intake should be considered.
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Botha MH. Pharmacological options for the protection of ovarian function in patients undergoing chemotherapy. SOUTHERN AFRICAN JOURNAL OF GYNAECOLOGICAL ONCOLOGY 2015. [DOI: 10.1080/20742835.2015.1030888] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022] Open
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GNRH agonists and antagonists in rescue for cyclophosphamide-induced ovarian damage: friend or foe? Arch Gynecol Obstet 2014; 291:1403-10. [DOI: 10.1007/s00404-014-3564-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2014] [Accepted: 11/25/2014] [Indexed: 10/24/2022]
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Orquevaux P, Masseau A, Le Guern V, Gayet V, Vauthier D, Boutin D, Wechsler B, Morel N, Guettrot-Imbert G, Pennaforte JL, Piette JC, Costedoat-Chalumeau N. [In vitro fertilization and systemic lupus erythematosus or antiphospholipid syndrome: An update]. Rev Med Interne 2014; 36:154-8. [PMID: 25217451 DOI: 10.1016/j.revmed.2014.08.004] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2014] [Accepted: 08/13/2014] [Indexed: 11/15/2022]
Abstract
Fertility is not impaired in systemic lupus erythematosus or antiphospholipid syndrome, but, similarly to the general population, these patients may undergo in vitro fertilization. This type of treatment increases the risk of lupus flare, thrombosis, and ovarian hyperstimulation syndrome. This review will focus on in vitro fertilization in systemic lupus erythematosus or antiphospholipid syndrome. Literature data are relatively scant with only 3 reported studies. The first one included 17 patients and 63 cycles of induction ovulation/in vitro fertilization leading to 25 % of lupus flare, no thrombosis, and 3 % of ovarian hyperstimulation syndrome. The second study included 10 patients and 40 cycles of in vitro fertilization showing 31 % of lupus flare, no thrombosis and no ovarian hyperstimulation syndrome. The last one included 34 patients and 83 procedures of in vitro fertilization leading to 8 % of flares, 5 % of thrombosis and no ovarian hyperstimulation syndrome. Interestingly, in this last study, half of the complications were explained by poor adherence to treatment. These data are reassuring but it is important to remember that in vitro fertilization should be scheduled and carefully supervised in the same way as the high-risk pregnancies occurring in these patients.
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Affiliation(s)
- P Orquevaux
- Service de médecine interne, centre de compétence maladies auto-immunes et systémiques rares, hôpital Robert-Debré, CHU de Reims, avenue du Général-Koenig, 51092 Reims cedex, France
| | - A Masseau
- Service de médecine interne, centre de compétence maladies auto-immunes et systémiques rares, Hôtel Dieu, CHU de Nantes, 1, place Alexis-Ricordeau, 44000 Nantes, France
| | - V Le Guern
- Service de médecine interne, centre de référence maladies auto-immunes et systémiques rares, pôle médecine, université René-Descartes, hôpital Cochin, AP-HP, 27, rue du Faubourg-Saint-Jacques, 75679 Paris cedex 14, France
| | - V Gayet
- Service de gynécologie-obstétrique, hôpital Cochin, AP-HP, 27, rue du Faubourg-Saint-Jacques, 75679 Paris cedex 14, France
| | - D Vauthier
- Service de gynécologie-obstétrique, groupe hospitalier Pitié-Salpêtrière, AP-HP, 47-83, boulevard de l'Hôpital, 75013 Paris, France
| | - D Boutin
- Service de médecine interne, groupe hospitalier Pitié-Salpêtrière, AP-HP, 47-83, boulevard de l'Hôpital, 75013 Paris, France
| | - B Wechsler
- Service de médecine interne, groupe hospitalier Pitié-Salpêtrière, AP-HP, 47-83, boulevard de l'Hôpital, 75013 Paris, France
| | - N Morel
- Service de médecine interne, centre de référence maladies auto-immunes et systémiques rares, pôle médecine, université René-Descartes, hôpital Cochin, AP-HP, 27, rue du Faubourg-Saint-Jacques, 75679 Paris cedex 14, France
| | - G Guettrot-Imbert
- Service de médecine interne, CHU Gabriel-Montpied, 58, rue Montalembert, 63003 Clermont-Ferrand, France
| | - J-L Pennaforte
- Service de médecine interne, centre de compétence maladies auto-immunes et systémiques rares, hôpital Robert-Debré, CHU de Reims, avenue du Général-Koenig, 51092 Reims cedex, France
| | - J-C Piette
- Service de médecine interne, groupe hospitalier Pitié-Salpêtrière, AP-HP, 47-83, boulevard de l'Hôpital, 75013 Paris, France
| | - N Costedoat-Chalumeau
- Service de médecine interne, centre de référence maladies auto-immunes et systémiques rares, pôle médecine, université René-Descartes, hôpital Cochin, AP-HP, 27, rue du Faubourg-Saint-Jacques, 75679 Paris cedex 14, France.
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Patel SS, Dodds EM, Echandi LV, Couto CA, Schlaen A, Tessler HH, Goldstein DA. Long-Term, Drug-Free Remission of Sympathetic Ophthalmia with High-Dose, Short-Term Chlorambucil Therapy. Ophthalmology 2014; 121:596-602. [DOI: 10.1016/j.ophtha.2013.09.009] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2013] [Revised: 08/26/2013] [Accepted: 09/08/2013] [Indexed: 11/24/2022] Open
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Rody A, Loibl S, von Minckwitz G, Kaufmann M. Use of goserelin in the treatment of breast cancer. Expert Rev Anticancer Ther 2014; 5:591-604. [PMID: 16111461 DOI: 10.1586/14737140.5.4.591] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Gonadotropin-releasing hormone analogs are, alongside tamoxifen, one of the most commonly used drugs in the treatment of pre-/perimenopausal endocrine-responsive breast cancer. Goserelin, as a principal agent of this class of drugs, is mainly investigated in clinical trials. The indirect comparison of goserelin with tamoxifen as a single drug in the adjuvant setting showed similar efficacy. Furthermore, goserelin is as effective as cyclophosphamide, methotrexate and 5-fluorouracil chemotherapy, and total endocrine blockade as a combination of gonadotropin-releasing hormone analog and tamoxifen showed a comparable benefit with anthracycline-containing adjuvant chemotherapy. Goserelin administered after cessation of chemotherapy leads to a further improvement and may be equieffective as tamoxifen or a combination of both. Data concerning taxane-based and dose-dense chemotherapy as well as combination of gonadotropin-releasing hormone analogs with third-generation aromatase inhibitors are still lacking (ongoing suppression of ovarian function, tamoxifen and exemestane, and premenopausal endocrine-responsive chemotherapy trials). Moreover, duration of therapy with gonadotropin-releasing hormone analogs (2-3 years or longer) is still a matter of debate. Palliative endocrine treatment is standard in the first-line therapy of patients without life-threatening disease and endocrine-responsive breast cancer. Treatment decisions depend upon adjuvant endocrine pretreatment. Clinical data regarding ovarian protection by synchronous use of gonadotropin-releasing hormone in young breast cancer patients receiving chemotherapy are incoherent.
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Affiliation(s)
- Achim Rody
- Department of Obstetrics and Gynecology, JW Goethe-University, Theodor-Stern-Kai 7, D-60590 Frankfurt, Germany.
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Bozzolo EP, Ramirez GA, Bonavida G, Lanzani C, Scotti R, Dell’Antonio G, Baldissera E, Canti V, Manfredi AA, Rovere-Querini P, Sabbadini MG. Efficacy and toxicity of treatments for nephritis in a series of consecutive lupus patients. Autoimmunity 2013; 46:537-46. [DOI: 10.3109/08916934.2013.817560] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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Management of women with systemic lupus erythematosus. Maturitas 2013; 75:207-14. [DOI: 10.1016/j.maturitas.2013.03.019] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2013] [Accepted: 03/10/2013] [Indexed: 01/30/2023]
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Li X, Kang X, Deng Q, Cai J, Wang Z. Combination of a GnRH agonist with an antagonist prevents flare-up effects and protects primordial ovarian follicles in the rat ovary from cisplatin-induced toxicity: a controlled experimental animal study. Reprod Biol Endocrinol 2013; 11:16. [PMID: 23452939 PMCID: PMC3598983 DOI: 10.1186/1477-7827-11-16] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2012] [Accepted: 01/31/2013] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND With the continuous improvement of surgery and chemotherapeutic treatments, many tumour patients increasingly achieve long-term survival and can even be completely cured. However, platinum-containing drugs, which are widely used to treat a variety of types of cancer, cause menstrual disorders and ovarian failure, which in turn lead to infertility. Thus far, gonadotropin releasing hormone (GnRH) agonist (GnRHa) and antagonist (GnRHant) are reported to act as protective agents of the ovary in chemotherapy through the inhibition of the female gonadal axis. Nevertheless, they both have disadvantages that limit their use. GnRHa causes a flare-up effect during the first week after administration, and no long-acting GnRHant agent is available. GnRHa combined with GnRHant may prevent the flare-up effect of GnRHa and rapidly inhibit the female gonadal axis. Several clinical studies with small sample sizes have reported controversial conclusions. In this strictly controlled animal study, we investigated the advantages of combination treatment with GnRHa and GnRHant. METHODS Rats aged 12 weeks were divided into six groups: Control, cisplatin (CDDP), GnRHa, GnRHant, Combination (sht, short-term) and Combination (lng, long-term) of GnRHa and GnRHant. The last four groups received Triptorelin (1 mg/kg·d, for 14 days), Cetrorelix (0.5 mg/kg·d, for 10 days), a combination of Triptorelin (1 mg/kg·d, for 10 days) and Cetrorelix (0.5 mg/kg·d, for 10 days) in the long-term group and for 3 days in the short-term group. The Control and CDDP groups received saline (1 ml/kg·d, for 10 day). Then, all groups apart from the Control group received cisplatin (1 mg/kg·d, for 10 days), and the Control group received another 10 days of saline as described above. Blood samples were collected to detect the serum levels of E2, LH and FSH. Observation of oestrous cyclicity was also performed after drug administration. Finally, bilateral ovaries were collected for histological study and follicle counting. RESULTS We observed a flare-up effect in rats treated with GnRHa, but not in any of the combination groups. The percentage of normal cyclicity increased from 0% in the CDDP group to 25.0%, 33.3%, 66.7% and 41.7%, in the GnRHa, GnRHant, combination (lng) and combination (sht) groups, respectively. Pretreatment with GnRHa, GnRHant and combination (lng) significantly protected the primordial follicles from destruction by preserving 57.6%, 63.4%, 87.1% and 60.4% of the follicles, respectively. CONCLUSIONS The combination of a GnRH agonist with antagonist completely prevented the flare-up effect and enhanced the protective effect of the ovary from cisplatin-induced gonadotoxicity in rats.
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Affiliation(s)
- Xiaoyan Li
- Department of Obstetrics and Gynecology, Union hospita, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiang Kang
- Department of Obstetrics and Gynecology, Union hospita, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Qingchun Deng
- Department of Obstetrics and Gynecology, Union hospita, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jing Cai
- Department of Obstetrics and Gynecology, Union hospita, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zehua Wang
- Department of Obstetrics and Gynecology, Union hospita, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Wong M, O'Neill S, Walsh G, Smith I. Goserelin with chemotherapy to preserve ovarian function in pre-menopausal women with early breast cancer: menstruation and pregnancy outcomes. Ann Oncol 2013; 24:133-8. [DOI: 10.1093/annonc/mds250] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
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Harward LE, Mitchell K, Pieper C, Copland S, Criscione-Schreiber LG, Clowse MEB. The impact of cyclophosphamide on menstruation and pregnancy in women with rheumatologic disease. Lupus 2012; 22:81-6. [DOI: 10.1177/0961203312468624] [Citation(s) in RCA: 60] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Background While cyclophosphamide (CYC) can save the life of a young woman with severe rheumatologic disease, it may lead to the long-term side-effects of infertility and premature menopause. We compared the reproductive health histories of young women with rheumatologic disease with and without prior CYC exposure to identify the impact of this medication on this important component of health. Methods This research includes a case-series study of women diagnosed with SLE, vasculitis, and scleroderma prior to age 35. Each patient completed a questionnaire about desired childbearing, menstrual regularity, infertility, and pregnancy history. Women with prior CYC therapy were queried about the use of gonadotropin-releasing hormone agonists (GnRH-a) for fertility preservation. The responses to this questionnaire were compared for women with and without CYC exposure. Results Of the 43 participants, 23 had prior CYC exposure and 20 were CYC naïve. The current age of these groups was similar (average age 32), but women with prior CYC were four years younger at diagnosis than women without CYC. More women with prior CYC had cessation of menses in the year prior to the study (30.4% vs 0%, p < 0.05). Of the women with prior CYC exposure, those with loss of menses were older at study enrollment, older at CYC treatment, and had a higher cumulative CYC dose than those with preserved menstruation. While more women with GnRH-a co-therapy during CYC had maintained menses, this difference did not reach statistical significance. Women with prior CYC without GnRH-a co-therapy had a higher frequency of nulliparity and had greater trouble conceiving than women with GnRH-a co-therapy. Few pregnancies were conceived following CYC exposure and all resulted in elective termination, miscarriage, or preterm birth. Conclusion In this cohort of young women with rheumatologic disease, more women with prior CYC than without had amenorrhea, nulliparity, and infertility. GnRH-a co-therapy may prevent these adverse effects of CYC.
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Affiliation(s)
- LE Harward
- Department of Medicine, Medical University of South Carolina, USA
| | - K Mitchell
- Department of Medicine, Duke University Medical Center, USA
| | - C Pieper
- Department of Biostatistics & Bioinformatics, Duke University Medical Center, USA
| | - S Copland
- Department of Obstetrics & Gynecology, Duke University Medical Center, USA
| | | | - MEB Clowse
- Department of Medicine, Duke University Medical Center, USA
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Marder W, Fisseha S, Ganser MA, Somers EC. Ovarian Damage During chemotherapy in Autoimmune Diseases: Broad Health Implications beyond Fertility. CLINICAL MEDICINE INSIGHTS. REPRODUCTIVE HEALTH 2012; 2012:9-18. [PMID: 23970822 PMCID: PMC3747568 DOI: 10.4137/cmrh.s10415] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Women with autoimmune diseases such as lupus, scleroderma, and vasculitis receiving cyclophosphamide for severe disease manifestations risk primary ovarian insufficiency(POI) due to gonadotoxicity of this therapy. In addition to loss of reproductive potential, POI is associated with increased risk of morbidity and mortality. Practitioners caring for women requiring gonadotoxic therapies should be familiar with long-term health implications of POI and strategies for ovarian preservation. Accumulating evidence supports the effectiveness of adjunctive gonadotropin releasing hormone analog (GnRH-a) for ovarian protection during gonadotoxic therapy in cancer and autoimmune populations. GnRH-a is less costly and invasive than assisted reproductive technologies used for achievement of future pregnancies, but is not Food and Drug Administration approved for ovarian preservation. This review focuses on POI comorbidities and strategies for mitigation of related sequelae, which can accumulate over decades of hypoesteogenism. These issues are arguably more pronounced for women with chronic autoimmune diseases, in whom superimposed POI further heightens risks of cardiovascular disease and osteoporosis. Therefore, even if future pregnancy is not desired, ovarian protection during gonadotoxic therapy should be a major goal of disease management.
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Affiliation(s)
- Wendy Marder
- Department of Internal Medicine, Division of Rheumatology, University of Michigan, Ann Arbor, MI, USA
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Blumenfeld Z. Preservation of ovarian function and fertility despite gonadotoxic chemotherapy. Expert Rev Endocrinol Metab 2012; 7:567-576. [PMID: 30780892 DOI: 10.1586/eem.12.40] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
The author aims to review the various strategies and avenues for fertility preservation despite gonadotoxic chemotherapy in young women. The recent increase in the survival of young patients has increased the worldwide attempts toward fertility preservation. The currently utilized methods are sperm cryopreservation and banking in male patients, and cryopreservation of embryos, unfertilized oocytes and ovarian tissue, as well as administration of gonadotropin-releasing hormone agonists (GnRH-a) before and during the gonadotoxic chemotherapy in young female patients. For those patients in whom pelvic irradiation is planned, ovariopexy is suggested. Since none of the suggested methods are ideal and none guarantees future fertility, a combination of several methods may optimize patients' chance of fertility preservation. GnRH-a co-treatment may reduce ovarian damage significantly in female patients treated with gonadotoxic chemotherapy. GnRH-a should be considered for women of reproductive age receiving gonadotoxic chemotherapy in addition to assisted reproduction and cryopreservation of embryos, oocytes and ovarian tissue.
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Affiliation(s)
- Zeev Blumenfeld
- a Reproductive Endocrinology, Department of Ob/Gyn, RAMBAM Healthcare Campus, The Rappaport Institute & Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel. ;
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Marder W, McCune WJ, Wang L, Wing JJ, Fisseha S, McConnell DS, Christman GM, Somers EC. Adjunctive GnRH-a treatment attenuates depletion of ovarian reserve associated with cyclophosphamide therapy in premenopausal SLE patients. Gynecol Endocrinol 2012; 28:624-7. [PMID: 22296584 PMCID: PMC3396751 DOI: 10.3109/09513590.2011.650752] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND We measured antimullerian hormone (AMH), a marker of ovarian reserve, in women with lupus treated with cyclophosphamide (CYC) (group I), CYC plus gonadotropin-releasing hormone agonist (GnRH-a) (group II) or neither (group III). We hypothesized that AMH would be diminished in women exposed to CYC versus women receiving adjunctive GnRH-a treatment or no CYC exposure. METHODS Forty-eight premenopausal lupus patients were retrospectively divided into three treatment groups: CYC alone (group I, n = 11), CYC + GnRH-a (group II, n = 10) and neither (group III, n = 27). Serum AMH levels between groups were compared using a nonparametric test (Wilcoxon rank-sum). Multiple linear regression adjusting for age was performed. RESULTS AMH (ng/mL) levels at the last collection were significantly lower in group I versus group III (mean ± SD: 0.18 ± 0.20 group I vs 1.33 ± 1.59 group III; p = 0.015), and versus group II (mean ± SD: 0.86 ± 1.06; p = 0.018). When centered on age 30 years, average AMH levels for group I, group II and group III were 0.20, 0.44 and 1.00, respectively. When adjusted for age, AMH between all groups was significantly different (p<0.0001). CONCLUSION Posttreatment AMH levels were significantly higher among patients receiving CYC + GnRH-a compared to CYC alone, suggesting that GnRH-a coadministration mitigates CYC-induced ovarian injury.
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Affiliation(s)
- W Marder
- Department of Internal Medicine, Division of Rheumatology, University of Michigan, Ann Arbor, MI 48109-5358, USA.
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Chuai Y, Xu X, Wang A. Preservation of fertility in females treated for cancer. Int J Biol Sci 2012; 8:1005-12. [PMID: 22904668 PMCID: PMC3421231 DOI: 10.7150/ijbs.4800] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2012] [Accepted: 07/29/2012] [Indexed: 12/17/2022] Open
Abstract
Advancements of diagnosis and treatment have substantially improved cancer survival rates in the last few decades. The increasing number of survivors focuses attention on long-term effects caused by cancer treatment and its impact on quality of life. Ovarian failure is one of the major sequelae of cytotoxic chemotherapy and/or radiotherapy in female children and reproductive-age women. Oncologists should address the patients about fertility preservation options before therapy. Embryo cryopreservation is the only well-established method for females in preserving fertility; however other strategies including ovarian suppression, ovarian transposition and cryopreservation of oocytes and ovarian tissue are still experimental. Patients need advice and to know which are the most practical options for them. This article reviews the available fertility preservation methods in women, and the related issues including normal physiology of the ovary, effect of anticancer therapy on fertility, role of the oncologist and ethics. We performed a MEDLINE search from 1971 to 2011 in a similar way as Jensen et al. 2011, using the following MeSH terms: antineoplastic agents; ovarian failure; premature; infertility, female; fertility preservation; child and cancer; reproductive technologies, assisted.
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Affiliation(s)
- Yunhai Chuai
- Department of Obstetrics and Gynecology, Navy General Hospital, Beijing, China
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Unnecessary life threatening complications after IVF in mixed connective tissue disease. J Assist Reprod Genet 2012; 29:573. [PMID: 22492224 DOI: 10.1007/s10815-012-9763-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2012] [Accepted: 03/26/2012] [Indexed: 10/28/2022] Open
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Henes M, Henes JC, Neunhoeffer E, Von Wolff M, Schmalzing M, Kötter I, Lawrenz B. Fertility preservation methods in young women with systemic lupus erythematosus prior to cytotoxic therapy: experiences from the FertiPROTEKT network. Lupus 2012; 21:953-8. [PMID: 22438026 DOI: 10.1177/0961203312442753] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
OBJECTIVES Despite new treatment options, some patients with systemic lupus erythematosus (SLE) need to be treated with the cytotoxic agent cyclophosphamide (CYC). Unlike malignant disease, there are no recommendations for ovarian protection in SLE. The clinical experience of the FertiPROTEKT network as well as recommendations after literature review will be presented in this paper. METHODS Retrospective analyses of counselling and treatment data from the FertiPROTEKT register with special respect to SLE patients under 40 years prior to planned CYC treatment. RESULTS A total of 2836 patients were advised prior to cytotoxic treatment in one of the FertiPROTEKT centres during January 2007 to November 2011. Of those, 68 patients (mean age 25 +/- 6.07 years) were counselled for severe SLE. Only five women did not make use of a fertility preservation method. Sixty-three patients (92.6%) decided in favour of a fertility preservation method. The largest proportion (91.2%) opted for treatment with a GnRH analogue. Ovarian tissue removal for cryoconservation was performed in 16 patients (25%). Stimulation therapy for cryoconservation of fertilized egg cells was performed in three patients (4.4%). CONCLUSIONS When counselling patients with SLE for fertility preservation one has to be aware of the disease-specific risks. According to the literature, a safe and effective option in SLE up to now has been the use of a GnRH analogue. Cryoconservation of ovarian tissue must still be seen as an experimental treatment, but as data on removal, cryoconservation, retransplantation and pregnancies are steadily rising, this presents a promising option for young SLE patients. Cryoconservation of oocytes must be very critically evaluated due to the need for a stimulation therapy and should only be performed after particular consideration of the individual risks.
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Affiliation(s)
- M Henes
- University Hospital for Women, University of Tuebingen Hospitals, Germany
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Blumenfeld Z. Chemotherapy and fertility. Best Pract Res Clin Obstet Gynaecol 2012; 26:379-90. [PMID: 22281514 DOI: 10.1016/j.bpobgyn.2011.11.008] [Citation(s) in RCA: 111] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2011] [Accepted: 11/25/2011] [Indexed: 11/29/2022]
Abstract
The overall increase in cancer prevalence and the significant increase in long-term survival have generated worldwide interest in preserving fertility in young women exposed to gonadotoxic chemo- and radiotherapy. Infertility represents one of the main long-term consequences of combination chemotherapy given for lymphoma, leukaemia and other malignancies in young women. The gonadotoxic effect of various chemotherapeutic agents is diverse, may involve a variety of pathophysiologic mechanisms, and is not unequivocally understood. Proliferating cells, such as in tissues with high turnover (i.e. bone marrow, gastrointestinal tract and growing ovarian follicles) are more vulnerable to the toxic effect of alkylating agents. These agents may also be cytotoxic to cells at rest, as they are not cell-cycle specific. Alkylating agents, the most gonadotoxic chemotherapeutic medications, cause dose-dependent, direct destruction of oocytes and follicular depletion, and may bring about cortical fibrosis and ovarian blood-vessel damage. The reported rate of premature ovarian failure after various diseases and chemotherapeutic protocols differ enormously, and depend mainly on the chemotherapeutic protocol used and age range of the woman. Several options have been proposed for preserving female fertility, despite gonadotoxic chemotherapy: ovarian transposition, cryopreservation of embryos, unfertilised metaphase-II oocytes and ovarian tissue, and administration of gonadotropin-releasing hormone agonistic analogs in an attempt to decrease the gonadotoxic effects of chemotherapy by simulating a prepubertal hormonal milieu. None of these methods is ideal and none guarantees future fertility in all survivors; therefore, a combination of methods is recommended for maximising women's chances of future fertility.
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Affiliation(s)
- Zeev Blumenfeld
- Department of Obstetrics and Gynaecology, RAMBAM Health Care Campus, The Rappaport Institute, Technion - Israel Institute of Technology, Haifa Israel.
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Preservación de la fertilidad en mujeres sometidas a tratamientos citotóxicos. Med Clin (Barc) 2011; 137:702-7. [DOI: 10.1016/j.medcli.2011.02.007] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2010] [Revised: 02/05/2011] [Accepted: 02/10/2011] [Indexed: 11/19/2022]
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Gonadotropin Releasing Hormone Agonists May Minimize Cyclophosphamide Associated Gonadotoxicity in SLE and Autoimmune Diseases. Semin Arthritis Rheum 2011; 41:346-52. [DOI: 10.1016/j.semarthrit.2011.05.008] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2010] [Revised: 05/25/2011] [Accepted: 05/25/2011] [Indexed: 01/08/2023]
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Chen H, Li J, Cui T, Hu L. Adjuvant gonadotropin-releasing hormone analogues for the prevention of chemotherapy induced premature ovarian failure in premenopausal women. Cochrane Database Syst Rev 2011:CD008018. [PMID: 22071842 DOI: 10.1002/14651858.cd008018.pub2] [Citation(s) in RCA: 68] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
BACKGROUND Chemotherapy has significantly improved prognosis for patients with malignant and some non-malignant conditions. This treatment, however, is associated with ovarian toxicity and gonadotropin-releasing hormone (GnRH) analogues may have a protective effect on the ovaries. The mechanism of action of GnRH is based on suppression of the gonadotropin levels to simulate pre-pubertal hormonal milieu and decrease utero-ovarian perfusion. OBJECTIVES To assess the efficacy and safety of GnRH analogues given before or in parallel to chemotherapy to prevent chemotherapy-related ovarian damage in premenopausal women with malignant or non-malignant conditions. SEARCH METHODS We searched the Cochrane Gynaecological Cancer Group Specialized Register (up to July 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 2, 2011); MEDLINE (1950 to July 2011); EMBASE (1980 to July 2011); and the Chinese Biomedicine Database (CBM) (1976 to July 2011). SELECTION CRITERIA Randomized controlled trials (RCTs), in all languages, which examined the effect of GnRH analogues for chemotherapy-induced ovarian failure in premenopausal women, were eligible for inclusion in the review. DATA COLLECTION AND ANALYSIS The review authors independently extracted data and assessed trial quality using the Cochrane risk of bias tool. We analyzed binary data using risk ratios (RRs) with 95% confidence intervals (CI) and for continuous data, we used the standardized mean difference (SMD) to combine trials. As there was substantial difference in the types of chemotherapy used, we applied the random-effects model in our analyses. We contacted study authors for additional information. MAIN RESULTS Included studies in this review showed that intramuscular/subcutaneous administration of GnRH agonists was effective in protecting menstruation and ovulation after chemotherapy (resumed menses: RR 1.90, 95% CI 1.30 to 2.79; amenorrhoea: RR 0.08, 95% CI 0.01 to 0.58; ovulation: RR 2.70, 95% CI 1.52 to 4.79), whereas intranasal administration of GnRH agonists had no protective effect on ovaries (resumed menses: RR 0.75, 95% CI 0.33 to 1.72; ovulation: RR 1.13, 95% CI 0.20 to 6.24). Pregnancy rates were not significantly different between groups (intramuscular/subcutaneous GnRH agonist: RR 0.21, 95% CI 0.01 to 4.09; intranasal GnRH agonist: RR 0.41, 95% CI 0.02 to 8.84). Ultrasound antral follicular count (AFC) was not significantly different between groups (SMD 1.11, 95% CI 0.32 to 1.90). AUTHORS' CONCLUSIONS The use of GnRH agonists should be considered in women of reproductive age receiving chemotherapy. Intramuscular or subcutaneous GnRH analogues seem to be effective in protecting ovaries during chemotherapy and should be given before or during treatment, although no significant difference in pregnancy rates was seen.
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Affiliation(s)
- Hengxi Chen
- Department of Obstetrics and Gynecology, West China Second University Hospital, West China Women’s and Children’s Hospital,Chengdu, China.
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